Frontiers in Cell and Developmental Biology最新文献

Background: Thalassemia is a common autosomal recessive disorder that may impact reproductive health and embryo development. However, limited information is available regarding the impact of thalassemia carrier status on embryo euploidy, developmental competence, and embryo availability. Therefore, this study aims to evaluate the effects on women with thalassemia by analyzing data from women undergoing IVF with PGT-A.

Methods: This retrospective cohort study included 2,110 women undergoing IVF with trophectoderm biopsy and PGT-A at Guangzhou Women and Children's Medical Center Liuzhou Hospital between January 2019 and December 2024. Women were grouped by thalassemia status (955 with thalassemia vs. 1,155 without). Statistical analyses included the use of the Mann-Whitney U test for continuous variables, Chi-square test for categorical variables, and regression models (Poisson for the number of euploid embryos and linear for the proportion of euploid embryos). Adjustments were made for potential confounders, and statistical significance was set at a two-sided p-value <0.05.

Results: After adjusting for key confounders including age, BMI, and AMH, no differences were observed between thalassemia and non-thalassemia women in embryo euploidy outcomes (adjusted RR for biopsied blastocysts: 1.06, 95% CI: 0.99-1.13; euploid embryos: 0.96, 95% CI: 0.86-1.08; proportion of euploid embryos: β = -0.03, 95% CI: -0.07-0.01). Although women with thalassemia initially showed higher numbers of biopsied blastocysts and euploid embryos in unadjusted analyses, these differences disappeared after adjustment. Further age-stratified analyses showed a slightly lower adjusted euploid proportion among thalassemia women aged 35-40 years (β = -0.07, 95% CI: -0.13 to -0.01), while no significant differences were observed in other age groups.

Conclusion: Overall, no significant differences were observed after adjustment for age, BMI, and AMH; however, a mild decrease in euploid proportion was noted among thalassemia women aged 35-40 years. These findings suggest that thalassemia does not generally impair embryo chromosomal integrity but that careful counseling may be warranted in this specific age group.

Background: High-fat diets are known to affect semen quality, potentially through metabolic and cellular stress mechanisms.

Objectives: This study investigates the impact of a high-fat diet on semen quality in male mice and identifies the underlying mechanisms involved.

Materials and methods: Thirty male C57BL/6J mice were randomly assigned to a control diet (CD) or HFD for 12 weeks. Sperm parameters and fertility were assessed by computer-assisted sperm analysis and mating trials. Testicular oxidative stress indices, autophagy- and apoptosis-related proteins were analyzed by biochemical assays and Western blot. Mitophagy (LC3B-Grp75 co-localization), tissue morphology (H&E, TUNEL, electron microscopy) and sperm DNA damage (DNA fragmentation index, 8-hydroxy-2'-deoxyguanosine [8-OHdG]) were further evaluated. Serum lipids and testosterone were measured by enzymatic assays and ELISA.

Results: HFD mice developed obesity, dyslipidemia, reduced testosterone, marked decreases in sperm count, progressive motility and normal morphology, and complete loss of fertility. Region-specific molecular alterations were observed along the reproductive tract: in epididymal caput, Beclin-1 and LC3B were upregulated and p62 downregulated, indicating enhanced autophagic flux; in cauda epididymis, pro-apoptotic markers increased and Bcl-2 decreased, consistent with augmented apoptosis; in testis, ATG5, Beclin-1, caspase-3 and Apaf-1 were elevated. HFD also increased testicular ROS and MDA, reduced SOD activity and mitochondrial membrane potential, and elevated sperm apoptosis, DNA fragmentation and 8-OHdG.

Conclusion: HFD induces a pathogenic cascade-oxidative stress, disrupted autophagy/mitophagy, and mitochondrial apoptosis-that collectively impair spermatogenesis and male fertility. Therapeutic strategies targeting antioxidant defenses, autophagic flux, and mitophagy may ameliorate obesity-related reproductive dysfunction.

Follistatin-like 1 (FSTL1) is an emerging multifunctional glycoprotein that plays a central role in cardiac repair following myocardial infarction (MI). While previous studies have explored its involvement in modulating inflammation, angiogenesis, and fibrosis, a cohesive mechanistic understanding remains incomplete. In this review, we provide a comprehensive synthesis of current findings and propose an integrated framework in which FSTL1 orchestrates post-infarction healing through multiple signaling cascades, including BMP/SMAD, PI3K/AKT, MAPK, and TGF-β pathways. We highlight its dual actions in both cardiomyocytes and cardiac fibroblasts, as well as its context-dependent interactions with mechanical cues and the immune microenvironment. Recent evidence suggests that FSTL1 may function as a key regulatory hub, coordinating sequential events such as inflammation resolution, extracellular matrix remodeling, and functional recovery. Together, these insights underscore the therapeutic promise of FSTL1 as a molecular target for enhancing cardiac repair and restoring myocardial integrity after infarction.

Prostate cancer (PCa) poses a significant threat to men's health worldwide, with persistently high incidence and mortality rates. Phthalates (PAEs), typical environmental endocrine disruptors (EDCs), are ubiquitous in the environment and readily accumulate in the human body due to their widespread use in plastics and consumer products. Their potential role in PCa development has drawn considerable attention. This review systematically summarizes the epidemiological associations between PAEs and PCa, their potential mechanisms of action, long-term risks, and corresponding prevention and control strategies. Epidemiological studies confirm that high-molecular-weight PAEs (e.g., di(2-ethylhexyl) phthalate [DEHP], dibutyl phthalate [DBP]) are significantly associated with increased PCa risk, with abdominally obese men identified as a susceptible population. Urinary PAE metabolites (e.g., mono(2-ethylhexyl) phthalate [MEHP], mono-n-butyl phthalate [MnBP]) serve as non-invasive biomarkers for assessing PAE exposure in prostate tissue. Mechanistically, PAEs may regulate PCa progression through multiple pathways, including disrupting the androgen/estrogen signaling balance, inducing epigenetic abnormalities (DNA hypomethylation, microRNA dysregulation), activating pro-proliferative/invasive signaling pathways (MAPK/AP-1, Wnt/β-catenin pathways), and inducing oxidative stress and facilitating epithelial-mesenchymal transition (EMT). Concurrently, PAEs may pose long-term carcinogenic risks through developmental programming and synergistic interactions with obesity to exacerbate PCa risk. Furthermore, this review proposes a multi-tiered prevention and control system comprising industrial source control, targeted protection of susceptible populations, occupational safeguards, and clinical integration. Future research should focus on core scientific questions, such as identifying key PAE subtypes that may be carcinogenic to the prostate, elucidating transgenerational epigenetic mechanisms underlying PAE-induced PCa susceptibility, and verifying the reversibility of PAE-obesity interactions in PCa development, to provide more substantial evidence for mitigating PAE-associated PCa risk.

The loss of chromosome 3p and the inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) were identified in clear cell renal cell carcinomas (ccRCC) over three decades ago. Since then, mutations in genes for the three chromatin modulators, polybromo 1 (PBRM1), SET domain-containing 2 (SETD2), and BRCA1-associated protein-1 (BAP1), have been recognized as common in ccRCC. Although these genomic alterations are central to understanding ccRCC's development, other deregulated cellular processes are also prominent in these tumors. Metabolic reprogramming is a key hallmark of this disease, characterized by various changes linked to the stabilization of hypoxia-inducible factors (HIF), including increased aerobic glycolysis, elevated lipid levels, and glutamine dependence for cell survival. Additionally, HIF-α stabilization plays a crucial role in regulating the immune system, thereby enhancing CD8⁺ T lymphocyte cytotoxicity. Immune checkpoint inhibitors (ICI) are now used as first-line treatments to target the often highly infiltrated tumor microenvironment of ccRCC. However, the effectiveness of ICI varies and is difficult to predict. Although emerging studies are beginning to provide insight, evidence suggests roles for PBRM1, SETD2, and BAP1 in metabolic regulation and in shaping the tumor immune microenvironment in ccRCC. Here, we review recent advances in this field and examine their impact on the management of ccRCC.

Kinetochores are essential molecular machines composed of dozens of protein subcomplexes that assemble onto specialized centromeric nucleosomes during every cell cycle prior to mitosis. During mitosis, the assembled kinetochores are responsible for maintaining load-bearing attachments to dynamic spindle microtubules, and for harnessing the forces generated by attached microtubules to organize and separate sister chromatids. Recent work shows that kinetochores can be reconstituted by assembling them in vitro onto centromeric DNAs in yeast whole cell lysates. By tethering individual centromeric DNAs to the surface of a coverslip, the assembly process and the microtubule-attachment activity of the assembled kinetochores can be studied at the single-molecule level. Kinetochores reconstituted in this manner are able to capture taxol-stabilized microtubules, with a strong intrinsic preference specifically for capturing microtubule plus ends. Super-resolution tracking further shows that the architecture of the assembled kinetochores changes in a microtubule polarity-dependent manner under external load. We anticipate that extensions of these approaches will uncover the molecular basis of the kinetochore's plus end-preference and, ultimately, will reveal how tension affects the arrangement of core subcomplexes and transient regulatory factors. Here we detail how to study individual kinetochores assembled from yeast whole cell lysate using single-molecule total internal reflection fluorescence microscopy.

This article comprehensively reviews the complex role of the Notch signaling cascade in cancer, as well as the regulatory mechanisms and potential anti-cancer effects of food functional ingredients on this pathway. The Notch signaling cascade is essential for maintaining normal cellular physiological processes and is closely associated with cancer initiation and progression; its abnormalities are linked to diverse biological behaviors of tumor cells, and it exhibits dual roles in both pro-cancer and anti-cancer properties. Food functional ingredients, including polyphenols, terpenoids, sulfur-containing compounds, vitamins, minerals, and other compounds, can precisely regulate the Notch signaling pathway via distinct molecular mechanisms and exert significant anti-cancer activity. In vitro cell experiments have elucidated the regulatory effects of these ingredients on the Notch pathway and their impacts on cancer cell phenotypes at the molecular level, while in vivo animal experiments further verified their efficacy in inhibiting tumor growth and metastasis. Although clinical research remains in its infancy, existing studies have provided directions for subsequent basic and clinical investigations-specifically, to further clarify the detailed mechanisms by which functional ingredients in food regulate the Notch signaling cascade and facilitate their clinical application in cancer treatment.

Background: With visual disturbances from vitreous opacities (VOs) and floaters drawing increasing attention, we analyzed real-world data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to characterize VO-associated drug profiles and inform clinical strategies for reducing VO-related complications.

Materials and methods: Disproportionality analysis was performed on FAERS reports (2004-2024) to identify VO-associated drugs. Drugs were then classified to assess the onset time and baseline characteristics. Multivariable logistic regression was used to evaluate confounders. The predictive performance was compared using six machine learning algorithms, with SHapley Additive exPlanations (SHAP) used for feature importance.

Results: Among 3,817 VO-related reports, 38 drugs were identified as independent risk factors, and they were mainly ocular, oncologic, hormonal, antimicrobial, and immunologic agents. Antimicrobial drugs had the earliest onset (mean 43.6 days), and hormonal drugs had the latest (mean 409.2 days). In the bootstrapped aggregating (BAG) model, the top predictors of VO were dexamethasone, reporter, time, brolucizumab, and age. The five highest-risk drugs were dexamethasone, brolucizumab, triamcinolone, faricimab, and fingolimod.

Conclusion: This first systematic real-world evaluation of VO-related adverse drug reactions identifies high-risk drugs, susceptible populations, and onset patterns, thus offering guidance for preventive medication strategies. The BAG model showed higher sensitivity in real-world analysis, suggesting potential for further research in VO and floater prevention and treatment.

Background: Acute Kidney Injury (AKI) poses a significant global health challenge, with increasing incidence and mortality rates, and profoundly impacts long-term outcomes, including progression to chronic kidney disease. Ischemia-reperfusion injury (IRI) is a major cause of AKI, in which hypoxia-inducible factor-1α (HIF-1α) plays a complex and dual role.

Methods: This review systematically analyzes the regulatory functions of HIF-1α in renal IRI, focusing on molecular mechanisms involving oxidative stress, apoptosis, inflammation, and tissue repair.

Results: Emerging evidence from preclinical studies demonstrates that HIF-1α orchestrates key adaptive responses in renal IRI, including the regulation of mitophagy, management of endoplasmic reticulum stress, and induction of metabolic reprogramming toward glycolysis.

Conclusion: Targeting HIF-1α represents a promising therapeutic strategy for AKI. Advances in HIF-1α-modulating therapies, particularly HIF prolyl hydroxylase inhibitors, offer novel avenues for both prevention and treatment. These findings underscore the potential for HIF-1α-centered therapies to mitigate AKI progression and improve clinical outcomes.